Prostate cancer is the second most common malignancy in men in the United States; only skin cancer occurs more frequently. Although most cases progress slowly and may never become clinically apparent, the disease is the second leading cause of cancer death in men and the most common cause of cancer death in male nonsmokers. Further, because of the disease’s strong association with age, the number of new cases and deaths from prostate cancer is expected to increase with the aging of the population.
Nearly all prostate cancer cases are adenocarcinomas; less than 3% are transitional cell carcinomas. Hormonal factors are important in the etiology of prostate cancer. Research studies have shown strong associations with testosterone and insulin-like growth factor I (IGF-1).
Symptoms often include dysuria, difficulty voiding, urinary frequency and retention, and hematuria. However, more than 80% of cases are asymptomatic and present with only an elevated prostate-specific antigen (PSA) level or firm nodule on digital rectal examination.
The most common sites of metastasis are lymph nodes and bone. A small number of cases present with symptoms of metastatic disease, such as vertebral back pain, renal failure due to ureteral obstruction, or weight loss.
Age: The prevalence of prostate cancer increases rapidly after middle age. The condition rarely occurs before age 45, whereas most men over 70 years show microscopic evidence of malignant cells.
Race: African-American men have the highest prostate cancer incidence and mortality of any demographic group. They also tend to have higher serum PSA levels and more advanced disease at diagnosis.
Genetics: Prostate cancer is likely influenced by several genetic factors. Men who have a first-degree relative with prostate cancer are twice as likely to develop the disease themselves. Early onset of prostate cancer in a first-degree family member further increases the risk.
The incidence of prostate cancer is also higher in families with breast cancer, and patients with BRCA1 or BRCA2 mutations appear to have a twofold- fivefold increased risk. Other inherited disorders like Lynch syndrome and Fanconi anemia also carry an increased risk for prostate cancer. ,
Obesity: In the Cancer Prevention Study II Nutrition Cohort that included 69,991 men, the risk for fatal prostate cancer was roughly 55% greater in men whose body mass indices (BMI) fell between 30 and 35, compared with men at a BMI below 25. In men treated with prostatectomy, obesity was also significantly associated with treatment failure. Obesity-related diseases (e.g., insulin resistance syndrome) appear to double the risk for prostate cancer.
High blood concentrations of IGF-1: IGF-I concentrations are associated with cancer risk and are influenced by both body weight and certain dietary intakes, as described in Nutritional Considerations below.
Lack of physical activity: In men aged 65 or older, a higher risk of advanced and fatal prostate cancer was found in those who were sedentary compared with those who were physically active. Other studies have concluded that a sedentary lifestyle is not associated with prostate cancer risk overall, but it may increase the risk for developing aggressive prostate cancer.
Screening for prostate cancer is controversial. Although PSA screening may provide a very small reduction in overall mortality, the high rate of false positives leads to unnecessary procedures. The oftentimes indolent nature of the disease itself may lead to unnecessary surgery and treatment as well. Currently, the USPSTF recommends that men not be routinely screened for prostate cancer. The American Cancer Society emphasizes shared decision making when deciding whether or not to screen.
The presence of an indurated area of the prostate, gland asymmetry, or a palpable nodule detected during digital rectal examination is suggestive, but malignancy may be present even with a normal prostate exam.
Most cases are detected by PSA screening. PSA is a very sensitive but nonspecific test. However, most elevated PSA results are false-positive for cancer and reflect chronic prostatitis or benign prostatic hyperplasia. This has led to considerable controversy about the meaning of an elevated PSA reading. Higher PSA velocity or shorter doubling time may help distinguish elevated PSA due to prostate cancer from that due to benign prostatic conditions. PSA also reliably reflects the effectiveness of treatment and disease activity after recurrence.
Prostate biopsy, usually via transrectal ultrasound, is necessary for definitive diagnosis.
Tumors are staged both clinically, according to the TNM (tumor, node, metastasis) classification, and pathologically, using the Gleason score.
Metastatic survey may include bone scan, skeletal MRI, CT scan of the abdomen and pelvis, and/or PET scan.
Due to the indolent nature of most cases of prostate cancer, active surveillance (careful monitoring of tumor growth without active treatment) can often be an acceptable option, particularly for older patients or those with low-grade disease.
Treatments for localized disease include radical prostatectomy, external beam radiation, internal radiation (brachytherapy), and cryotherapy. Radical prostatectomy and, to a lesser extent, external beam radiation often result in some degree of urinary incontinence and impotence. Brachytherapy tends to be associated with irritative voiding symptoms.
Gonadotropin-releasing hormone (GnRH) agonists (e.g., leuprolide), androgen receptor antagonists (e.g., flutamide, bicalutamide), and, to a lesser extent, orchiectomy are used as androgen-deprivation therapies to reduce circulating testosterone or to minimize the stimulation of testosterone on the prostate. These treatments may be used as primary or adjuvant therapy for localized disease but are most commonly used as a primary therapy for advanced disease or for palliation of symptoms from metastatic disease.
Chemotherapy is sometimes used for hormone-refractory prostate cancer and is under investigation as a treatment option for earlier stages of the disease.
Prostate cancer risk appears to be increasing worldwide, a trend that may be due in part to the globalization of Western eating habits, as well as increases in body weight. Conversely, evidence is accumulating that certain healthful dietary patterns may prevent prostate cancer. , ,19,20 Consumption of eggs, milk, and saturated fat is associated with increased risk.
The following principal issues have emerged in research on diet and prostate cancer:
Maintenance of a healthy weight. Obesity is linked with increased risk of developing aggressive prostate cancer, and adulthood weight gain is associated with prostate cancer mortality. Some evidence suggests that weight loss of > 10 pounds over 10 years in mid-adulthood may reduce prostate cancer incidence, and that weight loss with the help of exercise may reduce the incidence of aggressive cancers or prostate cancer-specific mortality.
Healthful dietary patterns. White men following a vegan diet were found to have a 35% lower risk for prostate cancer, compared with non-vegans, a difference that fell short of significance for African-Americans. 15 Men whose diets were more nutritious, as assessed by the Alternate Healthy Eating Index (AHEI-2010) and the Healthy Eating Index (HEI-2005), had a 7% and 8% lower risk for prostate cancer, respectively. 16 Components of these diets that have been associated with this reduced risk include legumes, lycopene, garlic, and cruciferous vegetables 28 (see below).
Animal Products and Increased Risk
Populations consuming diets high in animal products have higher risk of prostate cancer, compared with those following largely plant-based diets. In some studies, risk is associated with specific foods, including meat, , eggs and dairy products. , Others have revealed associations with other dietary sources of animal fat and saturated fat intake. The Health Professionals Follow-Up Study (HPFS) found that men who consumed 2.5 or more eggs per week had an 81% greater risk for fatal prostate cancer, when compared with those who consumed less than a half egg per week. In a pooled analysis of 15 other studies, men whose intake averaged a half egg per day or more had a 14% higher risk than those who consumed the lowest amount (1/10 of an egg/day). This same study found a roughly 18% greater risk for advanced prostate cancer in men with the highest red and processed meat intake when compared with those consuming the least. Previously, high intakes of red meat and dairy products were shown to be associated with twice the risk for metastatic prostate cancer compared with the lowest intakes.
Some have suggested that risk relates to processed meat only and that risk may be identified only in certain groups (e.g., black, rather than white, individuals). However, several studies have indicated that both red meat and chicken, when cooked at high temperatures, are associated with a significantly greater risk for prostate cancer, as is chicken with skin.
Several mechanisms have been proposed to explain these associations:
Androgenic effects. High-fat, low-fiber diets are associated with elevated blood testosterone concentrations, presumably as a result of either increased production or decreased excretion. , In turn, higher testosterone concentrations are associated with increased risk of prostate cancer. Men who adopt low-fat, high-fiber diets show about a 15% reduction in testosterone concentrations.,
Insulin-like growth factor. The association between animal product intake and prostate cancer risk may also be mediated by insulin-like growth factor 1 (IGF-1), a peptide with hormonal actions that increases with animal fat and animal protein consumption.
Carcinogens produced by cooking. Carcinogenic heterocyclic amines and polycyclic aromatic hydrocarbons tend to form as meat is cooked at high temperatures, and these are associated with increased risk of prostate cancer.
The NIH-AARP study suggested that nitrate and nitrite from processed meats or heme iron may also be implicated causally in the relationship between red meat and prostate cancer.
Dairy Product Intake and Increased Risk
Dairy products may play a role in prostate cancer risk that is distinct from that of other animal products. Two large Harvard University cohort studies (the Physicians’ Health Study and the Health Professionals Follow-Up Study), among several other epidemiologic studies, have shown significant increases in prostate cancer among the highest consumers of dairy products. , Although skim and low-fat milk were associated with nonaggressive cancers, whole milk was associated with significantly greater risks of progression to fatal disease after diagnosis and prostate cancer-specific mortality. 49 Similarly, in the Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study of 29,133 male smokers, the highest dairy consumers had a 26% higher risk compared with those consuming the least dairy products. Two mechanisms have been proposed to explain this association:
Hormonal effects of dairy products. Dairy products contain a variety of hormonally active compounds and may elevate blood concentrations of IGF-1.
Calcium’s ability to suppress vitamin D activation. Compared with men who have the lowest calcium intakes, those with the highest intakes appear to have as much as double the risk for developing prostate cancer. , , In the Health Professionals Follow-Up Study of approximately 48,000 men, those with calcium intakes between 1,500 and 1,999 mg/d had an 85% greater risk, and those with intakes above 2,000 mg/d had a roughly 245% greater risk, compared with those who had calcium intakes between 500 and 749 mg/d. Not all studies, however, have shown an association between calcium and prostate cancer.
The association between calcium and prostate cancer may be related to calcium’s tendency to suppress the activation of vitamin D from its prohormone form. Among vitamin D’s biological actions is maintenance of cellular differentiation within the prostate. In a sample of the Health Professionals Follow-Up Study cohort, higher calcium intake was associated with lower circulating 1,25(OH)2 vitamin D levels. The geographic distribution of prostate cancer mortality is known to be inversely associated with that of sunlight, and studies have found a protective effect of higher serum 25-OHD levels on prostate cancer risk. However, several other studies suggest that phosphorus may be equally responsible for increased prostate cancer risk. In a 24-year follow-up study of men in the HPFS, the association between high ( > 2,000 mg/d) calcium intake and prostate cancer were no longer significant when adjusted for phosphorus, and men with the highest intake of this mineral had a 12% higher risk for advanced, lethal, and high-grade cancers compared with those with the lowest phosphorus intakes.
Fruit and Vegetable Intake and Reduced Risk
Higher intake of lycopene-containing foods (predominantly tomato products) has been associated with a lower risk of prostate cancer. , Although not all studies support this finding, a pooled analysis of 15 prospective studies found a 35% lower risk for aggressive (not total) prostate cancer in men whose lycopene intake was highest, compared to the lowest intake group. 26 Lycopene may interfere with IGF-1 and other mediators of prostate cancer risk, such as androgen signaling, oxidative stress, and interleukin-6.
Intake of cruciferous vegetables (e.g., broccoli, cabbage, cauliflower, and Brussels sprouts) is also associated with reduced risk for prostate cancer, , perhaps because these foods can induce phase II detoxification enzymes, as well as cell-cycle arrest and apoptosis in prostate cancer cells.
Regular intake of allium vegetables (e.g., onions, leeks, scallions, and garlic) has also been associated with a decreased risk of prostate cancer. Individuals consuming the most allium vegetables had a nearly 20% lower risk, while those eating the most garlic had a nearly 25% lower risk. 27 It has been suggested that the possible anticancer effects of allium vegetables may involve immune stimulation and resultant release of interleukin-2, tumor necrosis factor, and interferon, and enhanced natural killer cell activity, in addition to pro-apoptosis effects, inhibition of cell cycle progression, and up-regulation of the tumor suppressor gene E-cadherin. 27
Additional Diet-Related Factors
Selenium. Studies indicate that individuals with adequate selenium status (attained through diet or low dose supplements) have a significantly lower risk for prostate cancer; however, high-dose selenium (140 μg/d) has been associated with a significantly higher risk for this cancer.
Alcohol. A large prospective cohort study found that alcohol was a minor factor in prostate cancer risk, except in men who tend to binge. Compared with abstainers, men who drank 105 g of alcohol (equivalent to 8-9 drinks) or more per week but who drank only 1-2 days each week had a 60% higher risk. Although some evidence suggests that liquor consumption increases risk more than beer or wine, other evidence indicates that risk increases with any type of alcohol.
Diet and Prognosis
Some studies have addressed diet’s possible influence on survival after diagnosis. Overall, evidence suggests that low-fat, plant-based diets may be helpful, presumably due to their beneficial effects on hormonal concentrations and on body weight.Obesity (BMI ≥ 30 kg/m2) has been significantly associated with treatment failure,
biochemical recurrence of treated prostate cancer, and with more aggressive cancer progression (i.e., high-grade disease, positive surgical margins, extraprostatic extension, and lymph node metastasis). Obese men had a 47% greater overall mortality compared to normal weight men, but those who had gained > 5% of initial weight nearly doubled their risk for prostate cancer-specific mortality. (See the Obesity chapter for healthful weight control measures.)
The Physicians’ Health Study concluded that a Western dietary pattern is associated with a significantly greater risk for prostate cancer-specific (and all-cause) mortality, when compared with a more healthful (“prudent”) pattern. 33 Similar results were found in a study that compared eating patterns high in a Dietary Inflammatory Index with diets low in proinflammatory foods.
Limited evidence suggests a substantial improvement in prostate cancer survival with diets that emphasize whole grains, legumes, and vegetables and avoid dairy products and meats. In a small clinical trial, diet treatment increased PSA doubling time from 6.5 months to 17 months.Similarly, in a randomized clinical trial using a vegan diet and stress reduction in 93 men with early prostate cancer who had elected not to undergo other treatment, the intervention group experienced a mean PSA reduction of 4%, compared with a 6% increase in the control group. None of the experimental group patients required medical treatment during the trial, but 6 control-group patients required conventional treatment, due to rising PSA concentrations or evidence of disease progression on magnetic resonance imaging.
Other investigators have found that a plant-based diet can significantly decrease the rate of PSA rise (or lead to a PSA reduction) in patients with recurrent prostate cancer. , The benefits of a low-fat, plant-based diet and exercise take on particular significance in light of the fact that cardiovascular disease remains a leading cause of death in prostate cancer patients. (See Coronary Heart Disease chapter.)
Observational studies show that higher saturated fat intakes are associated with a threefold higher prostate cancer mortality, compared with the lowest intake. , Similarly, in the Physicians’ Health Study, men who increased their intake of saturated fat by 5% or more after diagnosis had a nearly threefold higher risk for prostate cancer-specific mortality. Milk and other dairy products appear to have a particularly strong relationship with prostate cancer progression and mortality. 49
In the CAPSURE (Cancer of the Prostate Strategic Urologic Research Endeavor) study, eating the highest amounts of cruciferous vegetables was associated with a 59% decrease in risk for prostate cancer progression, when compared with men in the lowest intake group. A 15-year follow-up study of prostate cancer survivors found that men whose fruit and vegetable intake was above the median had a significantly higher probability for survival when compared with men whose intakes were below the median.
Moderate physical activity and stress reduction may be beneficial.
Limit alcohol to 0-2 drinks per day.
What to Tell the Family
Prostate cancer is increasingly common. Diet and lifestyle factors may influence the risk of developing the disease; particularly in its more aggressive and invasive forms. Cancer risk is not limited to the identified patient, however. A low-fat, plant-based diet and regular exercise habits, adopted early in life, may reduce cancer risk and improve the overall health of the entire family.
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